Structural valve degeneration in bioprosthetic heart valves

Bioprosthetic heart valves (BPHVs), valves made of biologic tissues rather than synthetic materials, have revolutionized the treatment of heart valve disease, which constitutes a significant health and economic burden in BC, Canada and around the world. BPHVs serve as an alternative to mechanical valves, which require lifelong treatment to prevent clotting and therefore lead to an increased risk of bleeding.

With the development of new transcatheter methods for delivery of BPHVs, they now represent the overwhelming majority of valves. Despite these successes, the long-term durability of BPHVs is not well established and remains a concerning potential limitation.

Dr. Sellers’ research will look to determine how BPHVs degenerate and potential strategies to assess this in patients. This will include using a combination of analysis of dysfunctional valves and novel imaging approaches using computed tomography (CT) imaging.

The results of this research will help determine the long-term durability of BPHVs and improve decision-making for patients with heart valve disease.

Effect of exogenous ketone supplementation on brain blood flow, metabolism, and cognitive function in Type II Diabetes

Exogenous ketone body (KB) ingestion is an emerging therapeutic strategy for combating the harmful health conditions associated with type 2 diabetes (T2D), including a heightened risk for neurological disease and cognitive decline.

Evidence from animal models and early studies in humans supports its potential; however, high-quality research trials examining the effect of KB ingestion on brain function in humans with T2D have not been performed.

Dr. Walsh’s research will investigate the acute (single dose) and short-term (14 day) effects of KB supplementation on aspects of brain function in people with T2D, including measures of cognition (i.e., memory and attention) and circulating growth factors related to cognition.

The results of this research will help determine the therapeutic potential of exogenous KB supplementation for improving brain, vascular, and metabolic health in people with T2D.

Improving resistance training in people with rheumatoid arthritis: A foundational behaviour change science approach

Resistance training has been shown to improve myriad health indicators, including quality of life, in people with rheumatoid arthritis (RA). However, resistance training participation rates among people with RA are remarkably low (1-14%), even in those with well-controlled disease. Anecdotally, unique barriers exist that prevent those with RA from participating in resistance training, including fear, health care provider knowledge, and functional limitation.

Resistance training-specific promotional efforts are sorely needed; however, understanding and research into changing resistance training behaviours is only in its early beginnings. The barriers to participating have yet to be scientifically explored and the state of behaviour change theory testing in resistance training behaviour is almost non-existent.

Dr. Ma’s will conduct a four-phase study to better understand the barriers and facilitators to resistance training, select promising behaviour change theories, and develop knowledge tools proposing resistance training interventions. The overarching aim is to launch the field of resistance training behaviour change, aid the uptake of guidelines, and improve health outcomes for patients with RA.  

Therapeutic efficacy of a novel enteral nutrition strategy in pediatric inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by chronic, relapsing inflammation of the gastrointestinal tract, and includes Crohn’s disease (CD) and ulcerative colitis (UC).

The gold standard induction therapy for treating active pediatric CD is “exclusive enteral nutrition” (EEN), which is a nutritionally complete liquid diet provided by tube feeding that excludes normal food intake. This nutritional strategy is superior to standard induction therapies; however, treatment must be maintained for 6-12 weeks to induce remission, and relapse rates are high after stopping EEN.

To date, EEN in pediatric patients with UC has not been shown to be effective and as a result is not regularly used. Also, the standard enteral formula does not contain fibre and is low in vitamin D, even though both factors lead to beneficial changes in gut bacteria and reduce inflammation in IBD.

Dr. Healey will recruit pediatric CD and UC patients to determine if enteral formula with fibre and concurrent oral vitamin D3 improves IBD beyond standard EEN and medications. Her research will also include undertaking animal studies to explore the mechanisms of this novel EEN strategy. The results of this research could lead to improved treatment strategies and outcomes for children with IBD.

Determining best practices in CBT implementation for pediatric OCD

Youth with obsessive compulsive disorder (OCD) often experience distressing experiences (for example, unwanted thoughts) which they try to prevent or relieve through obsessive strategies such as repeated hand-washing. Without treatment, OCD tends to remain a problem for youth and makes their lives very difficult.

Cognitive behavioral therapy (CBT) has been shown to reduce symptoms and improve quality of life for most youth with OCD. However, CBT is a broad term that can include different strategies and exactly which strategies are the best to use has not been carefully studied.

Dr. Selles’ research will involve implementing a five-day intensive CBT program for youth with OCD, comparing two different strategies for youth and two different strategies for therapist involvement. This study will examine how well the treatment works and compare the impact of these strategies on symptoms, child and family wellness, family preference, and cost.

This research will help bring a needed clinic service to British Columbia while providing therapists with clearer ideas about how to provide treatment in a way that will benefit youth with OCD the most.

Alpha-synuclein and its modified forms as biomarkers for dementia with Lewy bodies

Dementia with Lewy bodies is the second most common form of dementia following Alzheimer’s disease. This disease can be challenging to identify because symptoms can resemble those of Alzheimer’s disease, Parkinson’s disease, and/or mental illness. Currently, there is no test that can spot dementia with Lewy bodies and the only way to confirm the presence of this disease is by autopsy.

In this type of dementia, deposits known as Lewy bodies accumulate in the brain. Lewy bodies are formed by a protein inside neurons called alpha-synuclein. Alpha-synuclein is also found in cerebrospinal fluid, which is the fluid surrounding the brain and spinal cord. While we know that alpha-synuclein in cerebrospinal fluid is helpful for distinguishing dementia with Lewy bodies from Alzheimer’s disease, further work is needed to improve this test.

The goal of Dr. Singh’s research program is to develop a test that can identify dementia with Lewy bodies and distinguish and the disease from Alzheimer’s. She will create a diagnostic tool for clinical use to measure alpha-synuclein, and also explore modifications of alpha-synuclein that occur in disease that could improve our ability to identify dementia with Lewy bodies.

Personalizing myocarditis diagnostics through novel biomarkers

Myocarditis is defined as inflammation of the heart muscle, most often associated with viral infections. While the true occurrence of myocarditis is difficult to establish, it affects all ages and sexes and is a major cause of sudden death in young people.

Recognizing myocarditis in the clinic is challenging. Current tools for making a diagnosis are invasive (requiring access to heart tissue) and imprecise, leading to poor patient outcomes. Any delay in proper diagnosis may lead to dramatic measures like heart transplantation to ensure patient survival.

The goal of Dr. Hanson’s research is to develop tools to diagnose viral myocarditis more precisely, allowing for each patient to be treated in a timely fashion and on an individual basis. This will include applying knowledge from mouse models of viral myocarditis to humans. In these models, Dr. Hanson has so far discovered increased amounts of certain proteins in myocarditis hearts when compared to unaffected hearts. Previous work suggests these markers could improve our ability to identify patients with myocarditis, and may reliably distinguish those patients with viral infection in the heart muscle from others with inflammation but no infection.

This research will improve insight into what happens at the level of molecules during viral myocarditis, potentially identifying new ways to treat the disease. Ultimately, leading to the development of a non-invasive blood test to diagnose myocarditis, personalizing how patients with myocarditis are treated and managed.

Development of a novel biophotonics method to improve treatment and neurological outcomes in acute spinal cord injury

Acute spinal cord injury (SCI) is a devastating neurological condition resulting in permanent morbidity and impaired quality of life. In spite of advancements in the acute treatment of SCI, preventing neurological deficits in affected patients is highly limited. The hemodynamic management of acute SCI patients to maintain blood supply and maximize oxygenation of the injured spinal cord tissue is currently one of the few aspects of critical care in which clinicians can improve neurologic outcomes. However, optimizing the hemodynamic management in acute SCI is limited and challenging due to the lack of a real-time means for monitoring spinal cord blood flow, oxygenation, and hydrostatic pressure.

The overall objective of Dr. Shadgan's research is to develop a novel optical method, using an implantable optical sensor and system that work based on near-infrared spectroscopy (NIRS) to provide real-time measurements of spinal cord hemodynamics in acute human SCI. Such a tool would provide information to guide clinicians in their treatment decisions and allow them to personalize the hemodynamic management of acute SCI patients to optimize neurologic outcomes. This program includes a sequence of preclinical studies aimed to translate this approach to human SCI patients. Dr. Shadgan's research program will also include the training of highly qualified personnel, intellectual property protection of the method and system, and knowledge translation.

Prevention of severe bacterial infections in children by optimizing protection through vaccination

Dr. Sadarangani's  research focuses on preventing severe illness and death in children by ensuring best use of vaccines to protect against three serious infections (meningococcal, pneumococcal, pertussis) which cause blood poisoning, meningitis and whooping cough.

Vaccines have reduced these infections, but we dont know if we are usng the optimal number and timing of dses. Sadarangani's goals are to ensure optimal use of these vaccines and aid development of future vaccines.

The project will:

  1. Compare the current three doses of pneumococcal vaccine given to infants against two doses. If there is no difference using two doses would mean fewer injections and lower cost.
  2. Compare the response to meningococcal vaccine in adolescents who have received 1, 2 or 3 previous doses, and compare the three available vaccines to identify any differences between them.
  3. Compare the effectiveness of pertussis vaccinefor whooping cough at different times of pregnancy to confirm the best time to immunize to protect the infant
  4. Examine the genetics of the pneumococcal bacteria to understand its transmission and evolution.

This research will improve vaccine schedules and help design future vaccines, ensuring that children continue to be protected against these devastating infections.

Integrative genomics to identify novel therapeutics and biomarkers for COPD

Chronic obstructive pulmonary disease (COPD) affects 300 million people worldwide and is the third leading cause of death, responsible for over 3 million deaths per year. It is the number one reason why adults end up in hospitals. However, we do not have good drugs to treat patients with COPD. This is because we do not fully understand how and why COPD develops and progresses.

Smoking can cause COPD but not all smokers get the disease; our genes also play a role. Identifying which genes cause some people to get COPD or lead to disease worsening over time will allow us to understand these processes more and to develop new drugs to treat the disease.

This project will use sophisticated analysis tools called integrative genomics. First, we will identify regions of our DNA that are important for COPD risk and worsening over time. This will be done through studying DNA regions from thousands of subjects with and without the disease and on whom we have information on how well their lungs work. We will then identify the function of these DNA regions by uncovering their effect on gene products and proteins in tissues that are important and relevant for COPD such as lung and blood. These genes and their products will be tested in laboratories to confirm the findings. The goal is to use this information to monitor disease and will additionally allow us to interfere with these gene products to treat disease.